The long-term objective is to develop gene therapy vectors that deliver hair-pin ribozymes for the treatment of HIV infection. Although great success has been achieved in the development of ribozymes that have antiviral activities comparable to small molecule drugs, gene delivery to primary cells has been a fundamental problem. In an effort to overcome this obstacle, these investigators have begun to develop cell-type specific targetable vectors for CD4 and CD34 cell surface proteins. This technology is based on incorporation of "targeting moieties" into the adeno-associated virus vector (AAV) cap proteins as fusion molecules. Thus far, some success has been achieved by fusion of a single-chain antibody variable region (ScF) with the N-terminus of AAV Vp2 protein. Their short-term goal in this proposal is to optimize the transduction efficiency of these vectors. To achieve this goal, they will address the following questions: 1) Does changing the capsid protein or terminus for fusion give improved transduction efficiency? 2) Does decreasing the size of the targeting molecule from a 250 amino acid ScF to a 20 amino acid synthetic binding peptide improve transduction efficiency? 3) Can mutations which eliminate AAV binding to its normal receptor be incorporated into the targetable vectors with mono-tropic transduction of cells of interest? PROPOSED COMMERCIAL APPLICATION: NOT AVAILABLE